We have begun a clinical protocol to determine if resident lymphocytes in non-small cell lung cancer are reactive with tumor specific mutated neo-antigens and if so, whether they can be therapeutic if given patients using methods recently developed in the Surgery Branch (Tran et al, Science 2014). We are studying ways to sequence the genome of a patient's lung cancer, identify all mutated proteins, redisplay them effectively to the T-cells in their tumors and search for T-cells that can react to these mutated neo-antigens. We then wish to develop ways to isolate or enrich them, grow them and readminister them for therapy. This study also is attempting to find T-cell receptors that could be used to target commonly shared antigens in other patients (see Project #3).